This program describes a three-year training program for the development of an academic career in craniofacial research. The principal investigator has completed clinical training in Pediatrics and Neonatology and has been expanding her experience in research in developmental biology. This award will help her to develop advanced skills in craniofacial research and provide opportunities needed to establish a successful independent career in developmental biology research. Paul Trainor, PhD, will mentor the scientific development of the principal investigator, and will provide instruction in the techniques of embryo manipulation. Dr. Trainor has extensively researched the role of cranial neural crest cells and their relationship to the mesoderm in craniofacial development -and has developed unique techniques for the evaluation of gene function in early mouse embryos. His laboratory provides the ideal environment for examining the relationship of the early endothelium to neural crest and branchial arch development. The Stowers Institute, in collaboration with Children's Mercy Hospital, provides the appropriate setting for this program. The collaborative environment and the proximity of renowned researchers in related fields provide the opportunity for interaction and feedback, while the availability of extensive core facilities and state-of the- art equipment allows for comprehensive and unique research. Research for this program will focus on understanding the role of the cranial mesoderm, and specifically its endothelial derivatives, on cranial neural crest and branchial arch development. The proposed experiments will examine the effect of endothelial gene overexpression and inhibition on neural crest and branchial arch formation and differentiation, and will identify extrinsic regulators of endothelial development, focusing on the effects of FGF8 and SHH. The specific aims include: 1) Functionally characterizing the role of the cranial mesoderm and endothelial derivatives on cranial neural crest cell development, 2) Functionally characterizing the role of the cranial mesoderm and endothelial derivatives on branchial arch development, and 3) Identifying and evaluating the extrinsic regulators that pattern the formation of the cranial mesoderm and its endothelial derivatives. This characterization of endothelial development and interaction with neural crest cells will help to define the role of the cranial mesoderm in craniofacial development and may ultimately help define many craniofacial defects seen in human syndromes such as DiGeorge and Velocardiofacial syndrome.